Long-Lasting Induction of Astrocytic Basic Fibroblast Growth Factor by Repeated Injections of Amphetamine: Blockade by Concurrent Treatment with a Glutamate Antagonist

Flores, Cecilia; Rodaros, Demetra; Stewart, Jane

doi:10.1523/jneurosci.18-22-09547.1998

Cited by 76 publications

(53 citation statements)

References 63 publications

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“…A possible explanation is that changes in netrin-1 receptor expression are involved in the development, but not the expression of sensitization. For instance, we have demonstrated previously that the same AMPH treatment regimen as the one used in the current study results in an enduring upregulation of bFGF expression in the VTA, but not in DA terminal regions (Flores et al, 1998). Another possibility is that AMPH does induce changes in NAcc netrin-1 receptor expression, but that these changes only become evident at a later time point.…”

mentioning

confidence: 57%

Regulation of netrin-1 receptors by amphetamine in the adult brain

Yetnikoff¹,

Labelle‐Dumais²,

Flores³

2007

Neuroscience

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Netrin-1 is a guidance cue molecule fundamental to the organization of neuronal connectivity during development. Netrin-1 and its receptors, deleted in colorectal cancer (DCC) and UNC-5 homologues (UNC-5), continue to be expressed in the adult brain, although neither their function nor the kinds of events that activate their expression are known. Two lines of evidence suggest a role for netrin-1 in amphetamine-induced dopamine plasticity in the adult. First, DCC is highly expressed by adult dopamine neurons. Second, adult mice with reduced DCC levels do not develop amphetamine-induced behavioral sensitization. To explore the role of netrin-1 in amphetamine-induced plasticity, we examined the effects of sensitizing treatment regimens of amphetamine on DCC and/or UNC-5 protein expression in the adult rat. These treatments produced striking and enduring increases in DCC and UNC-5 expression in the cell body, but not terminal regions, of the mesocorticolimbic dopamine system. Notably, neuroadaptations in the cell body region of mesocorticolimbic dopamine neurons underlie the development of sensitization to the effects of amphetamine. Furthermore, these localized amphetamine-induced changes were prevented by co-treatment with an N-methyl-D-aspartate receptor antagonist, a treatment known to block the development of amphetamine-induced sensitization of behavioral activation, dopamine release and motivated behavior. Using immunohistochemistry, we showed that both DCC and UNC-5 receptors are highly expressed by adult mesocorticolimbic dopamine neurons. These results provide the first evidence that repeated exposure to a stimulant drug such as amphetamine affects netrin-1 receptor expression in the adult brain. Taken together, our findings suggest that changes in netrin-1 receptor expression may play a role in the lasting effects of exposure to amphetamine and other stimulant drugs. Keywords sensitization; DCC; UNC-5; plasticity; dopamine; glutamate Stimulant drugs, such as amphetamine, induce locomotor-activating and rewarding effects by increasing extracellular dopamine (DA) levels in striatal terminal regions. These behavioral and neurochemical effects become sensitized when the drug is administered repeatedly (Stewart and Badiani, 1993;Kalivas and Stewart, 1991;Vezina 2004). Key features of sensitization, including its gradual development and persistence over time, CIHR Author Manuscript CIHR Author Manuscript CIHR Author Manuscriptsuggest underlying alterations in the organization of mesocorticolimbic DA circuitry. Indeed, stimulant-induced modifications in dendritic structure have been identified in midbrain DA perikarya and in striatal and cortical DA terminal regions, suggesting alterations in patterns of synaptic connectivity within these regions (Berlanga et al., 2006;Kolb et al., 2003;Mueller et al., 2006; Kolb, 1997, 1999;Sarti et al., 2007). Although the mechanisms underlying amphetamine-induced plasticity of DA circuitry are unclear, it is known that the development of sensitization depends on (1) ...

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mentioning

confidence: 57%

Regulation of netrin-1 receptors by amphetamine in the adult brain

Yetnikoff¹,

Labelle‐Dumais²,

Flores³

2007

Neuroscience

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“…How FGF signaling, hyperactivity, and the dopamine system are related is not clear. However, the ligands FGF1 and FGF2 are present in regions pertinent to the dopamine system during normal development and are expressed in adult brain (Bean et al, 1992) at levels that can be experimentally modified (Chadi et al, 1994;Flores et al, 1998Flores et al, , 2000Moroz et al, 2003;Bustos et al, 2004;Fumagalli et al, 2006). Furthermore, hyperactivity in mice has also been associated with attenuation of Fgfr1 signaling and loss of glutamatergic pyramidal neurons in frontal and temporal cortex (Shin et al, 2004), and transgenic mice expressing dominant-negative Fgfr1 in dopaminergic neurons display schizophrenia-like syndromes associated with high dopamine levels and hyperactivity (Klejbor et al, 2006).…”

Section: Discussionmentioning

confidence: 99%

Mice with Conditional Inactivation of Fibroblast Growth Factor Receptor-2 Signaling in Oligodendrocytes Have Normal Myelin But Display Dramatic Hyperactivity when Combined with Cnp1 Inactivation

Kaga¹,

Shoemaker²,

Furusho³

et al. 2006

J. Neurosci.

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Fibroblast growth factor receptors (Fgfr) comprise a widely expressed family of developmental regulators implicated in oligodendrocyte (OL) maturation of the CNS. Fgfr2 is expressed by OLs in myelinated fiber tracks. In vitro, Fgfr2 is highly upregulated during OL terminal differentiation, and its activation leads to enhanced growth of OL processes and the formation of myelin-like membranes. To investigate the in vivo function of Fgfr2 signaling by myelinating glial cells, we inactivated the floxed Fgfr2 gene in mice that coexpress Cre recombinase (cre) as a knock-in gene into the OL-specific 2Ј,3Ј-cyclic nucleotide phosphodiesterase (Cnp1) locus. Surprisingly, no obvious defects were detected in brain development of these conditional mutants, including the number of OLs, the onset and extent of myelination, the ultrastructure of myelin, and the expression level of myelin proteins. However, unexpectedly, a subset of these conditional Fgfr2 knock-out mice that are homozygous for cre and therefore are also Cnp1 null, displayed a dramatic hyperactive behavior starting at ϳ2 weeks of age. This hyperactivity was abolished by treatment with dopamine receptor antagonists or catecholamine biosynthesis inhibitors, suggesting that the symptoms involve a dysregulation of the dopaminergic system. Although the molecular mechanisms are presently unknown, this novel mouse model of hyperactivity demonstrates the potential involvement of OLs in neuropsychiatric disorders, as well as the nonpredictable role of genetic interactions in the behavioral phenotype of mice.

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“…bFGF has been implicated in the reorganization and dendritic growth of neurons after drug administration (Mueller et al, 2006), suggesting that bFGF contributes to the structural changes underlying the development and maintenance of drug abuse (Flores et al, 1998;Mueller et al, 2006). Indeed, endogenous bFGF in the VTA is required for the induction of locomotor sensitization by amphetamine (Flores et al, 2000a) and stimulant administration increases bFGF mRNA expression in the PFC (Fumagalli et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

Blocking Infralimbic Basic Fibroblast Growth Factor (bFGF or FGF2) Facilitates Extinction of Drug Seeking After Cocaine Self-Administration

Hafenbreidel

Twining

Todd

et al. 2015

Neuropsychopharmacol

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Drug exposure results in structural and functional changes in brain regions that regulate reward and these changes may underlie the persistence of compulsive drug seeking and relapse. Neurotrophic factors, such as basic fibroblast growth factor (bFGF or FGF2), are necessary for neuronal survival, growth, and differentiation, and may contribute to these drug-induced changes. Following cocaine exposure, bFGF is increased in addiction-related brain regions, including the infralimbic medial prefrontal cortex (IL-mPFC). The IL-mPFC is necessary for extinction, but whether drug-induced overexpression of bFGF in this region affects extinction of drug seeking is unknown. Thus, we determined whether blocking bFGF in IL-mPFC would facilitate extinction following cocaine self-administration. Rats were trained to lever press for intravenous infusions of cocaine before extinction. Blocking bFGF in IL-mPFC before four extinction sessions resulted in facilitated extinction. In contrast, blocking bFGF alone was not sufficient to facilitate extinction, as blocking bFGF and returning rats to their home cage had no effect on subsequent extinction. Furthermore, bFGF protein expression increased in IL-mPFC following cocaine self-administration, an effect reversed by extinction. These results suggest that cocaine-induced overexpression of bFGF inhibits extinction, as blocking bFGF during extinction permits rapid extinction. Therefore, targeted reductions in bFGF during therapeutic interventions could enhance treatment outcomes for addiction.

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Long-Lasting Induction of Astrocytic Basic Fibroblast Growth Factor by Repeated Injections of Amphetamine: Blockade by Concurrent Treatment with a Glutamate Antagonist

Cited by 76 publications

References 63 publications

Regulation of netrin-1 receptors by amphetamine in the adult brain

Regulation of netrin-1 receptors by amphetamine in the adult brain

Mice with Conditional Inactivation of Fibroblast Growth Factor Receptor-2 Signaling in Oligodendrocytes Have Normal Myelin But Display Dramatic Hyperactivity when Combined with Cnp1 Inactivation

Blocking Infralimbic Basic Fibroblast Growth Factor (bFGF or FGF2) Facilitates Extinction of Drug Seeking After Cocaine Self-Administration

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